I presented a JI paper about the role of CD28null CD4+ T cells in autoimmune diseases.

1. Inflammation-Autoimmunity Journal Club
December 15th, 2016
Presented by Thi Nguyen

2. CD4+ CD28null T cells
• Unique subset of helper T cells, found in many chronic
inflammatory patients PBMC+ tissue such as autoimmune
disease (RA, MS), chronic viral infection (HIV, CMV) and
atherosclerosis.
• Frequency correlates with disease severity.
• ≠ naïve T cells who loses CD28 and become anergic, these null
cells are ag-experienced and has limited ag diversity (probably
developed from repeated ag stimulation).
• Secrete high amount of inflammatory cytokines (both Th1 and
Th2 and TNF-α)
• Unique feature: a helper T cell with high expression of
cytolytic enzymes. (Also express NK receptor such as NKG2D).

3. CD4+ CD28null T cells

4. Study background
• This group discovered the unusual CD4+CD28 null
subset in RA and MS patients compared to HC.
• Goal of study:
1. Characterize phenotype of this CD28null subset
2. Test ag-reactivity to different set of foreign and
auto-ag in RA and MS.

5. STUDY COHORT

6. Figure 1: Characterize CD4+ CD28 null cells

7. Figure 2: Tissue infiltrating properties of CD4+ CD28null cells

8. Figure 3: In- vitro proliferation in different conditions:
Figure 4a: In- vitro proliferation (with ag)

9. Figure 4 b,c,d: In- vitro proliferation of CD28null cells- Quantification

10. Table III: CD4+ CD28null in-vitro cytokine secretion

11. Figure 5: TCR BV gene expression in CMV (and some with anti-CD3) stimulated
CD28 null cells

12. Figure 6: CD4+ CD28 null cells are resistant to Treg regulation

13. SUMMARY
CD4+CD28null cells in HC, RA and MS:
- ag-experienced
- lower CD27 and CD25 expression
- cytolytic ezymes
- higher tissue-infiltrating property
- autologous proliferation
- CMV reactive >>> known auto-ag.
- CMV reactive CD28 null cells possibly have undergone clonal
expansion