UMMS Affiliation

Immunology and Microbiology Program, Graduate School of Biomedical Sciences; Department of Microbiology and Physiological Systems

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Document Type



Bacterial Infections and Mycoses | Immunology and Infectious Disease | Microbiology


CD4 T cells are essential for immunity to tuberculosis because they produce cytokines, including interferon-gamma. Whether CD4 T cells act as "helper" cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.


CD4 T cell help, CD4 T cells, CD8 T cells, CTL, T cell exhaustion, immunity, infection, interferon gamma, lung, mycobacterium tuberculosis

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Copyright 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Lu YJ, Barreira-Silva P, Boyce S, Powers J, Cavallo K, Behar SM. CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection. Cell Rep. 2021 Sep 14;36(11):109696. doi: 10.1016/j.celrep.2021.109696. PMID: 34525366; PMCID: PMC8466141. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

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PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.