CD4(+) T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes in Rag2(-/-) mice.
Accumulating evidence supports a role of T cells in behavioral stress responsiveness. Our laboratory previously reported that lymphocyte deficient Rag2(-/-) mice on a BALB/c background display resilience to maladaptive stress responses when compared with immune competent mice in the predator odor exposure (POE) paradigm, while exhibiting similar behavior in a cued fear-conditioning (FC) paradigm. In the present study, Rag2(-/-) mice on a C57BL/6 background were assessed in the same behavioral paradigms, as well as additional tests of anxiety and depressive-like behavior. Furthermore, the effects of naïve CD4(+ ) T cells were evaluated by adoptive transfer of functional cells from nonstressed, wild-type donors to Rag2(-/-) mice. Consistent with our prior results, Rag2(-/-) mice displayed an attenuated startle response after POE. Nevertheless, reconstitution of Rag2(-/-) mice with CD4(+ ) T cells did not modify startle reactivity. Additionally, in contrast with our previous findings, Rag2(-/-) mice showed attenuated fear responses in the FC paradigm compared to wild-type mice and reconstitution with CD4(+ ) T cells promoted fear learning and memory. Notably, reconstitution with CD4(+ ) T cells had anxiolytic and antidepressant-like effects in Rag2(-/-) mice that had not been previously stressed, but had no effect after POE. Taken together, our results support a role of CD4(+ ) T cells in emotionality, but also indicate that they may promote fear responses by enhancing learning and memory processes.
a Department of Psychiatry, Laboratory of Behavioral Neuroimmunology , University of Maryland School of Medicine , Baltimore , MD , USA ;|b Department of Veterans Affairs, Research and Development Service , VA Maryland Health Care System , Baltimore , MD , USA.
Sarah M
SM
Clark
a Department of Psychiatry, Laboratory of Behavioral Neuroimmunology , University of Maryland School of Medicine , Baltimore , MD , USA ;
Jennifer A
JA
Soroka
a Department of Psychiatry, Laboratory of Behavioral Neuroimmunology , University of Maryland School of Medicine , Baltimore , MD , USA ;
Chang
C
Song
a Department of Psychiatry, Laboratory of Behavioral Neuroimmunology , University of Maryland School of Medicine , Baltimore , MD , USA ;
Xin
X
Li
a Department of Psychiatry, Laboratory of Behavioral Neuroimmunology , University of Maryland School of Medicine , Baltimore , MD , USA ;|b Department of Veterans Affairs, Research and Development Service , VA Maryland Health Care System , Baltimore , MD , USA.
Leonardo H
LH
Tonelli
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003863:Depression / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology; D005239:Fear / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D013216:Reflex, Startle / Q000502:physiology
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse
Adaptive immunity; anxiety; depression; fear memory; lymphocytes; startle reactivity