Immune cell depletion is a valuable tool for understanding the roles of specific immune cell populations in various disease models and for developing targeted therapies. By selectively depleting certain immune cell types, researchers can gain insights into their functions and contributions to pathological processes. In this article, we will discuss the proteins that can be targeted for immune cell depletion in vivo, focusing on the different immune cell types, depletion methods, and the antibody clones that have been shown to effectively deplete them.

1. CD4+ T Cells

CD4+ T cells are critical players in adaptive immunity, orchestrating immune responses and providing help to other immune cells. To deplete CD4+ T cells in vivo, researchers commonly target the CD4 molecule itself.

Antibody Clones:

– GK1.5: A rat anti-mouse CD4 monoclonal antibody widely used for CD4+ T cell depletion [1].

– YTS191: A rat anti-mouse CD4 monoclonal antibody that effectively depletes CD4+ T cells [2].

2. CD8+ T Cells

CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), play a crucial role in eliminating virus-infected cells and tumor cells. Depletion of CD8+ T cells is often achieved by targeting the CD8 molecule.

Antibody Clones:

– YTS169.4: A rat anti-mouse CD8 monoclonal antibody commonly used for CD8+ T cell depletion [3].

– 53-6.72: Another widely used rat anti-mouse CD8 monoclonal antibody for in vivo depletion [4].

3. B Cells

B cells are responsible for humoral immunity, producing antibodies and contributing to immune memory. To deplete B cells in vivo, researchers often target the CD20 molecule, which is expressed on the surface of mature B cells.

Antibody Clones:

– 18B12: A mouse anti-mouse CD20 monoclonal antibody that efficiently depletes B cells in vivo [5].

– 5D2: A rat anti-mouse CD20 monoclonal antibody used for B cell depletion studies [6].

4. Natural Killer (NK) Cells

NK cells are innate lymphocytes that play a critical role in antiviral and antitumor immunity. Depletion of NK cells can be achieved by targeting the NK1.1 molecule in mice.

Antibody Clones:

– PK136: A mouse anti-mouse NK1.1 monoclonal antibody widely used for NK cell depletion [7].

– asialo-GM1: A polyclonal antibody that recognizes asialo-GM1, a glycolipid expressed on the surface of NK cells and some T cell subsets [8].

5. Macrophages

Macrophages are versatile innate immune cells involved in phagocytosis, inflammation, and tissue homeostasis. Depletion of macrophages can be achieved by targeting the CSF1R (colony-stimulating factor 1 receptor) or by using liposomal clodronate.

Antibody Clones:

– AFS98: A rat anti-mouse CSF1R monoclonal antibody that effectively depletes macrophages in vivo [9].

Liposomal Clodronate:

– Liposomal clodronate is a bisphosphonate encapsulated in liposomes that, when phagocytosed by macrophages, induces apoptosis and selective depletion [10].


Selective immune cell depletion is a powerful approach for dissecting the roles of specific immune cell populations in various disease models and for developing targeted therapies. By targeting proteins such as CD4, CD8, CD20, NK1.1, and CSF1R, researchers can effectively deplete CD4+ T cells, CD8+ T cells, B cells, NK cells, and macrophages, respectively. The choice of antibody clone or depletion method depends on the specific research question and the immune cell type of interest. As our understanding of immune cell biology continues to grow, new targets and depletion strategies may emerge, further expanding the toolbox for in vivo immune cell depletion studies.


1. Cobbold SP, et al. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984;312(5994):548-551.

2. Wofsy D, et al. Reversal of advanced murine lupus in NZB/NZW F1 mice by treatment with monoclonal antibody to L3T4. J Immunol. 1987;138(10):3247-3253.

3. Cobbold SP, et al. Depletion of CD8+ T cells in vivo with monoclonal antibodies: a role for non-specific recycling. Transplantation. 1988;46(2 Suppl):120S-123S.

4. Ledbetter JA, Herzenberg LA. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63-90.

5. Hamaguchi Y, et al. The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice. J Immunol. 2005;174(7):4389-4399.

6. Sarikonda G, et al. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice. PLoS One. 2013;8(2):e54712.

7. Seaman WE, et al. Use of monoclonal antibodies in the study of natural killer cells. Immunol Rev. 1981;57:221-256.

8. Kasai M, et al. In vivo effect of anti-asialo GM1 antibody on natural killer activity. Nature. 1981;291(5813):334-335.

9. MacDonald KP, et al. An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation. Blood. 2010;116(19):3955-3963.

10. Van Rooijen N, Sanders A. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods. 1994;174(1-2):83-93.


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