ADHESION AND DEGRANULATION PROMOTING ADAPTER PROTEIN (ADAP) PROMOTES CD8 T CELL DIFFERENTIATION AND RESIDENT MEMORY FORMATION AND FUNCTION DURING AN ACUTE INFECTION1
During acute infections, naïve antigen-specific CD8 T cells are activated and differentiate into effector T cells, the majority of which undergo contraction after pathogen clearance. A small population of CD8 T cells persists as memory to protect against future infections. We investigated the role o...
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Published in | The Journal of immunology (1950) Vol. 197; no. 6; pp. 2079 - 2089 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
12.08.2016
|
Online Access | Get full text |
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Summary: | During acute infections, naïve antigen-specific CD8 T cells are activated and differentiate into effector T cells, the majority of which undergo contraction after pathogen clearance. A small population of CD8 T cells persists as memory to protect against future infections. We investigated the role of adhesion and degranulation promoting adapter protein (ADAP) in promoting CD8 T cell responses to a systemic infection. Naïve antigen-specific CD8 T cells lacking ADAP exhibited a modest expansion defect early after
Listeria monocytogenes
or vesicular stomatitis virus infection but comparable cytolytic function at the peak of response. However, reduced numbers of ADAP-deficient CD8 T cells were present in the spleen after the peak of the response. ADAP deficiency resulted in a greater frequency of CD127
+
CD8 memory precursors in secondary lymphoid organs during the contraction phase. Reduced numbers of ADAP-deficient KLRG1
−
resident memory CD8 T cell (T
RM
) precursors were present in a variety of non-lymphoid tissues at the peak of the immune response, and consequently the total numbers of ADAP-deficient T
RM
were reduced at memory time points. T
RM
cells that did form in the absence of ADAP were defective in effector molecule expression. ADAP-deficient T
RM
cells exhibited impaired effector function after Ag re-challenge, correlating with defects in their ability to form T:APC conjugates. However, ADAP-deficient T
RM
cells responded to TGFβ signals and recruited circulating memory CD8 T cells. Thus, ADAP regulates CD8 T cell differentiation events following acute pathogen challenge that are critical for the formation and select functions of T
RM
cells in non-lymphoid tissues. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.1501805 |