Investigating T Cell Development in Patients with Low CD4 Counts

* INCLUSION CRITERIA

ICL patients:

1. Documented history of idiopathic CD4 lymphocytopenia as defined by CD4 T cell count \<300 cells/microL or \<20% of total T lymphocytes on 2 occasions at least 6 weeks apart in the absence of any illness or medications accounting for CD4 lymphocytopenia. Although the protocol will primarily enroll ICL patients who are lymphopenic at the time of enrollment, up to three patients who had clear documentation of ICL in the past and are currently not lymphopenic may still be enrolled for comparative purposes. For similar comparative purposes, we may enroll up to five participants with known or unknown immunological-defects that may be affecting lymphocyte homeostasis or function, irrespective of CD4 T cell counts, including people with history of infectious diseases or other conditions that are typically seen in ICL \[i.e. cryptococcal diseases, mycobacterial diseases, HPV-related diseases, histoplasmosis, progressive multifocal leukoencephalopathy or herpesviruses associated diseases (Varicella-zoster virus diseases, cytomegalovirus diseases, or Kaposi's sarcoma) and autoimmune diseases\].
2. Hemoglobin \>=9 g/dL
3. Human T-lymphotropic virus Type 1 (HTLV-1) and HTLV-2 seronegative Persons with documented history of ICL in whom genetic analysis revealed inherited defects that are either known or suspected to be involved in development, maturation, or homeostasis of hematopoietic cells

Healthy volunteers: white blood cell count \>2500/microL and hemoglobin \>=12.5 g/dL

ICL patients, patients with similar immunological defects, and healthy volunteers:

1. Age 18-65 years
2. Weight at least 50 kg but less than 167 kg and \<175% ideal body weight (due to lack of data regarding appropriate dosing of plerixafor)
3. Ability to give informed consent
4. Capacity and willingness to adhere to study procedures, including scheduled follow-up visits
5. Willingness to have blood samples stored for future research
6. Willingness to undergo HLA testing
7. Established primary care provider
8. HIV-1 and HIV-2 seronegativity and plasma HIV-1 RNA polymerase chain reaction (PCR) below the limit of detection
9. Adequate venous access to allow leukapheresis without use of a central line or a large volume blood draw
10. Participant agrees to be heterosexually inactive or consistently use effective birth control (e.g., barrier methods, oral contraceptives, intrauterine devices, vasectomy) for the duration of study participation and for approximately 8 weeks after the last dose of G-CSF. This is necessary for both male and female participants.
11. For women of childbearing potential:

    1. Negative serum or urine pregnancy test

EXCLUSION CRITERIA

1. Active uncontrolled infection at the time of enrollment
2. Current autoimmune conditions requiring systemic (oral, injection, or other parenteral) therapy
3. History of vasculitis
4. Current or history of hematologic or lymphoid malignancy (leukemia)
5. History of splenomegaly or current splenomegaly on exam or ultrasound (for ICL patients and patients with similar immunological defects)
6. History of hypersensitivity to plerixafor and/or G-CSF
7. Recent use of a systemic immune-modulatory agent which, in the opinion of the investigator, may interfere with the scientific integrity of the study.
8. Thrombocytopenia (platelets \<100,000 cells/microL)
9. Hepatitis B and C seropositivity (HBsAg positive and anti-HCV positive) Need for anticoagulant medication (e.g., warfarin, heparin), other than aspirin, clopidogrel, or other antiplatelet agent
10. Creatinine clearance \<50 mL/min including end-stage renal disease requiring hemodialysis
11. Symptomatic coronary artery disease
12. Uncontrolled hypertension (i.e., resting systolic blood pressure \>160 mmHg or resting diastolic blood pressure \>90 mmHg) despite pharmacologic antihypertensive treatment confirmed with a second blood pressure measurement done later on the same day
13. Cardiac, pulmonary, thyroid, renal, hepatic, neurological (central or peripheral) disease or disorder of hemostasis requiring therapy and considered to be significant by the protocol team
14. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
15. Currently receiving lithium due to contraindication of co-administration of G-CSF with lithium
16. Past or current psychiatric illness that, in the opinion of the investigator, would interfere with protocol adherence or the ability to give written informed consent
17. Any illness or condition that, in the opinion of the investigator, may substantially increase the risk associated with participation in the study or compromise the scientific objectives
18. Participation in a clinical protocol which includes an intervention that, in the opinion of the investigator, may affect the results of the current study
19. Previous history of anaphylactic reaction to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
20. Female who is breast-feeding.